Cementocytes Express Receptor Activator of the Nuclear Factor Kappa-B Ligand in Response to Endodontic Infection in Mice

Introduction: Although studies have recently shown that osteocytes embedded in mineralized bone matrix play an important role in bone diseases, the participation of cementocytes in apical periodontitis has not been evaluated. The aim of the present study was to evaluate the possible involvement of cementocytes in the development of apical periodontitis. Methods: Apical periodontitis was experimentally induced in the lower first molars of wild-type mice by pulp exposure to the oral environment. At 0, 7, 21, and 42 days after pulp infection, the animals were euthanized, and the jaws were prepared for analysis under conventional and fluorescence microscopy (morphologic and morphometric analysis), immunohistochernistry and immunofluorescence (receptor activator of nuclear factor kappa-B [RANK], receptor activator of the nuclear factor kappa-B ligand [RANKL], and osteoprotegerin [OPG]), enzyme histochemistry (osteoclasts and cementoclasts), and real-time polymerase chain reaction (RANK, RANKL, OPG, and cathepsin K). Results: At 7, 21, and 42 days after pulp exposure, there was a progressive increase in periodontal ligament, cementum and bone resorption areas, osteoclasts, and cementoclast counts as well as higher messenger RNA levels of RANK, RANKL, OPG, and cathepsin K. In intact teeth, cementocytes and osteocytes did not express RANKL. After infection, RANKL was strongly expressed in cementocytes, but not in osteocytes, and its expression increased with lesion progression. Conclusions: Our findings show that cementocytes express RANKL in response to endodontic infection and may be involved in the pathogenesis of apical periodontitis.